• Korean Journal of Head & Neck Oncology
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• v.27 no.1
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• pp.59-65
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• 2011

Background and Objectives : Papillary thyroid carcinoma(PTC) frequently metastasize to the regional neck, however, lateral neck lymph node metastasis is less common. The aim of this study is to investigate clinical and immunohistochemical features of PTC with lateral LN metastasis, and determine the predictive factors for lateral LN metastases. Material and Methods : We undertook a retrospective study of 83 patients treated between January 2007 and December 2009 for PTC by thyroidectomy with or without lateral neck dissection. The following criteria were used to study the clinical predictive value of lateral LN. metastases : sex, age, tumor size, multifocality, extracapsular spread(ECS) and lymphovascular emboli. Immunohistochemical staining for VEGF-A, VEGF-C, Bax, Bcl-2, Cyclin D1, Cyclin E, $p27^{kip1}$ and $p57^{kip2}$ was performed, and quantified blindly by three pathologists who had no clinical information of the patients. Immunohistochemical expression was scored as high(>50% of cells stained) or low(0-49%). Results : With use of univariate and multivariate analysis, tumor size(>2cm) and ECS were independent correlates of lateral LN metastasis in PTC. Expression of VEGF-C, Bax, and Cyclin D1 in the PTC with lateral LN metastasis was scored higher than in PTC without lateral LN metastasis(p<0.05). Conclusion : The important risk factors for lateral LN metastasis in PTC are primary tumor size and the presence of ECS. And expression of VEGF-C, Bax and cyclin D1 may be considered of lateral LN metastatic potential in PTC.

• Korean Journal of Clinical Laboratory Science
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• v.45 no.2
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• pp.66-72
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• 2013

Fine Needle Aspiration Biopsy Cytology (FNABC), which is known as the most accurate and cost-effective method for diagnosis of the thyroid nodule, may still result in indeterminate cases that are cellular paucity and show minor nuclear atypia. However, most cases are associated with suspicion of papillary thyroid carcinoma (PTC). A B-type Raf kinase (BRAF) mutation was found in about half of PTCs which is currently helping us to differentiate malignancies from benign lesions. Cases studied included 46 histological, confirmed PTC cases. FNABC 102 cell paucity and 74 atypia benign cases were previously diagnosed as suspicious of PTC using cytologic examination. These cases were analyzed for BRAF mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with a new restriction enzyme. In this study, the sensitivity and specificity were calculated and, BRAF mutation was detected by means of a histological method in 23 of 46 cases of PTC and no mutation was found in 22 cases. However, one case was not detected. In using FNABC, BRAF mutation was detected in 6 of 102 cases in cell paucity and in 11 of 74 cases in the atypia. Two cases were not detected in the atypia. The sensitivity and specificity of PCR-RFLP in FNABC were 60% and 97.4% respectively. Assessment of Formalin Fixed Paraffin Embedding (FFPE) block demonstrated similarly a 51.1% positive and 48.9% negative in PTC. Evaluation of BRAF mutation revealed high specificity and low sensitivity in using FNABC method. This study suggests that BRAF mutation analysis should be useful for the clinical diagnosis of PTC in FNABC with cytological findings suspicious for PTC.

• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.121-125
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• 2005

Objectives: To investigate the role of MMP-2 and TIMP-2 in the invasion and metastasis of thyroid papillary microcarcinomas. Materials and Methods: We performed immunohistochemical study on MMP-2 and its tissue inhibitor (TIMP-2) using tissue microarrays containing 2 cores of 40 microPTC and 8 non-neoplastic thyroid tissue. The expression intensity was semiquantitatively scored as -, ${\pm}$, +1, +2, and +3. Results: Both MMP-2 and TIMP-2 expression was observed in all tumors(100%) and in 1 of 8 non-neoplastic tissue(12.5%), and the positive staining was restricted to the epithelial cells. In 17 and 23 tumors with or without extrathyroid invasion, respectively, 8(47%) and 10(43%) cases showed moderate to strong(+23) positivity for MMP-2. TIMP-2 expression was moderate to strong in 13 cases(76%) and 16 cases(70%) in each group. In multifocal and solitary tumors, 3 of 6(50%) and 11 of 21(52%) cases showed moderate to strong MMP-2 expression, and 5/6(83%) and 15/21(71%) showed moderate to strong TIMP-2 expression. Conclusion: There is no relationship between MMP-2 or TIMP-2 expression and extrathyroid invasion or tumor multifocality in papillary microcarcinoma of the thyroid gland.

• Korean Journal of Radiology
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• v.24 no.12
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• pp.1284-1292
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• 2023

Objective: We investigated the impacts of computed tomography (CT) added to ultrasound (US) for preoperative evaluation of patients with papillary thyroid carcinoma (PTC) on staging, surgical extent, and postsurgical survival. Materials and Methods: Consecutive patients who underwent surgery for PTC between January 2015 and December 2015 were retrospectively identified. Of them, 584 had undergone preoperative additional thyroid CT imaging (CT + US group), and 859 had not (US group). Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for 14 variables and balance the two groups. Changes in nodal staging and surgical extent caused by CT were recorded. The recurrence-free survival and distant metastasis-free survival after surgery were compared between the two groups. Results: In the CT + US group, discordant nodal staging results between CT and US were observed in 94 of 584 patients (16.1%). Of them, CT accurately diagnosed nodal staging in 54 patients (57.4%), while the US provided incorrect nodal staging. Ten patients (1.7%) had a change in the extent of surgery based on CT findings. Postsurgical recurrence developed in 3.6% (31 of 859) of the CT + US group and 2.9% (17 of 584) of the US group during the median follow-up of 59 months. After adjustment using IPTW (580 vs. 861 patients), the CT + US group showed significantly higher recurrence-free survival rates than the US group (hazard ratio [HR], 0.52 [95% confidence interval {CI}, 0.29-0.96]; P = 0.037). PSM analysis (535 patients in each group) showed similar HR without statistical significance (HR, 0.60 [95% CI, 0.31-1.17]; P = 0.134). For distant metastasis-free survival, HRs after IPTW and PSM were 0.75 (95% CI, 0.17-3.36; P = 0.71) and 0.87 (95% CI, 0.20-3.80; P = 0.851), respectively. Conclusion: The addition of CT imaging for preoperative evaluation changed nodal staging and surgical extent and might improve recurrence-free survival in patients with PTC.

• Korean Journal of Head & Neck Oncology
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• v.35 no.2
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• pp.11-17
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• 2019

Background/Objectives: Papillary thyroid carcinoma (PTC) has generally an indolent character with a good prognosis. However, recurrence remains a major concern for the patients during their lifetime. Despite the slowly progressing character of PTC, recurrence can occur within a short period after initial surgery. This study aimed to determine the clinical findings and cause of recurrence in patients who underwent re-operative surgery due to neck node recurrence by reviewing the CT (computed tomographic) scan imaging of the recurrence of PTC retrospectively. Materials & Methods: We reviewed the medical records of patients referred to Ajou University Hospital from January 2002 to January 2018. All patients had re-operative surgery due to neck node recurrence and CT scan results of preoperative evaluation and postoperative follow up. Over this period, 110 patients who underwent re-operation due to neck node recurrence with a CT scan were included in our cohort, resulting in a total of 220 re-operations. Results: The time from initial operation to first re-operation was examined in 110 patients. The median time to re-operation was 28 months, with a range of 4 months to 186 months. Most re-operations (82.7%) occurred within the first five years, 43.6% were in the first two years from the initial surgery. The result of the retrospective CT review showed newly developed cases (21,19.1%), missed diagnosis cases (42,38.2%), real recur cases after surgery (33,30.0%), and remnant lymph nodes (LNs) cases (14,12.7%). We further sub-analyzed 14 cases with remnant LNs. Reasons for remnant LNs included insufficient operation (N=5) and beyond general surgical extent. (N=9). Conclusion: Re-operation due to cervical lymph node recurrence is mostly a persistent disease. They included a missed diagnosis and incomplete operation. These finding may reduce the reoperation of cervical lymph node recurrence by accurate preoperative evaluation and complete surgical resection at the initial surgery.

• Journal of the Korean Society of Radiology
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• v.84 no.1
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• pp.185-196
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• 2023

Purpose This study aimed to investigate radiomics analysis of ultrasonographic images to develop a potential biomarker for predicting lymph node metastasis in papillary thyroid carcinoma (PTC) patients. Materials and Methods This study included 431 PTC patients from August 2013 to May 2014 and classified them into the training and validation sets. A total of 730 radiomics features, including texture matrices of gray-level co-occurrence matrix and gray-level run-length matrix and single-level discrete two-dimensional wavelet transform and other functions, were obtained. The least absolute shrinkage and selection operator method was used for selecting the most predictive features in the training data set. Results Lymph node metastasis was associated with the radiomics score (p < 0.001). It was also associated with other clinical variables such as young age (p = 0.007) and large tumor size (p = 0.007). The area under the receiver operating characteristic curve was 0.687 (95% confidence interval: 0.616-0.759) for the training set and 0.650 (95% confidence interval: 0.575-0.726) for the validation set. Conclusion This study showed the potential of ultrasonography-based radiomics to predict cervical lymph node metastasis in patients with PTC; thus, ultrasonography-based radiomics can act as a biomarker for PTC.

• Radiation Oncology Journal
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• v.35 no.2
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• pp.112-120
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• 2017

Purpose: To evaluate the effect of adjuvant external beam radiation therapy (EBRT) on local failure-free survival rate (LFFS) for papillary thyroid cancer (PTC) invading the trachea. Materials and Methods: Fifty-six patients with locally advanced PTC invading the trachea were treated with surgical resection. After surgery, 21 patients received adjuvant EBRT and radioactive iodine therapy (EBRT group) and 35 patients were treated with radioactive iodine therapy (control group). Results: The age range was 26-87 years (median, 56 years). The median follow-up period was 43 months (range, 4 to 145 months). EBRT doses ranged from 50.4 to 66 Gy (median, 60 Gy). Esophagus invasion and gross residual disease was more frequent in the EBRT group. In the control group, local recurrence developed in 9 (9/35, 26%) and new distant metastasis in 2 (2/35, 6%) patients, occurring 4 to 68 months (median, 37 months) and 53 to 68 months (median, 60 months) after surgery, respectively. Two patients had simultaneous local recurrence and new distant metastasis. There was one local failure in the EBRT group at 18 months after surgery (1/21, 5%). The 5-year LFFS was 95% in the EBRT group and 63% in the control group (p = 0.103). In the EBRT group, one late grade 2 xerostomia was developed. Conclusion: Although, EBRT group had a higher incidence of esophagus invasion and gross residual disease, EBRT group showed a better 5-year LFFS. Adjuvant EBRT may have contributed to the better LFFS in these patients.

• The Korean Journal of Cytopathology
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• v.19 no.1
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• pp.27-33
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• 2008

Although subacute granulomatous thyroiditis(SGT) is usually diagnosed clinically, papillary carcinoma or other thyroid conditions must be considered in the differential diagnosis. We retrospectively reviewed the clinical and fine-needle aspiration(FNA) cytologic findings seen in 10 SGT cases to decide what are the most reliable cytologic findings and the most helpful molecular tools for reaching a confident cytologic diagnosis. The most representative smear slides were retrieved to perform immunocytochemistry for cytokeratin 19(CK19) and Ret protein. Five papillary carcinomas(PTCs) were included as controls. The constant and typical cytologic findings of SGT were multinucleated giant cells(MGCs) (100%), epithelioid granulomas(90%), an inflammatory dirty background(90%) and plump transformed follicular cells(80%) without fire-flare cells, oncocytic cells or transformed lymphocytes. The immunoreactivities for CK19(37.5%) and Ret(10%) of the follicular cells of SGT were less than those(CK19 and Ret:100%) of PTC. CK19 immunoreactivity of the MGCs was seen in only one case of PTC. There was no significant difference between CK19 and Ret immunocytochemical staining for the MGCs of both SGT and PTC. The results of this study demonstrate that the cytological diagnosis of SGT can be improved by employing a combination of the typical and constant diagnostic cytological features and immunocytochemical results.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3213-3217
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• 2013

Background: P-glycoprotein (Pgp), encoded by the multidrug resistance 1 (MDR1) gene, is an efflux transporter which plays an important role in pharmacokinetics. The current preliminary study was designed to determine associations between a germ-line polymorphism in the MDR1 gene with differentiated thyroid carcinoma (DTC). Materials and Methods: In the current case-control study, 60 differentiated thyroid cancers (DTC)- 45 papillary TC (PTC), 9 follicular TC(FTC) and 6 well-differentiated tumors of uncertain malignant potential (WDT-UMP) were examined. Results were compared to a healthy control group (n=58) from the same population. Genomic DNA was extracted from peripheral blood with EDTA and the target gene was genotyped by real-time PCR. Results: Carriers of the variant allele of MDR1 exon 26 polymorphism were at 2.8-fold higher risk of DTC than the control group (odds ratio [OR]: 0.3805, 95% confidence interval [Cl]: 0.1597-0.9065 (p> 0.046). Conclusions: Presented results suggest that the MDR1 3435TT genotype might influence risk of development of DTC and that the CC genotype might be linked to a poor prognosis. Large-scale studies are now needed to validate this association.

• Korean Journal of Head & Neck Oncology
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• v.32 no.1
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• pp.13-19
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• 2016

Background : The 2015 American thyroid association (ATA) guidelines greatly expanded section on risk stratification of thyroid cancer. Definition of "Low risk of recurrence" has expanded, by inclusion of small volume lymph node involvement, such as less than 5 lymph node metastases each smaller than 2mm in central compartment. Purpose : We evaluated the number of positive nodes, Positive node ratio (PNR), recurrence, and radioablation therapy. Also, evaluated the safety of omitting strategy of radioablation after total thyroidectomy with PTC, especially on low-PNR N1a patients compared with high-PNR N1a patients. Methods : Consecutive 147 N1a and 216 N0 patients who underwent total thyroidectomy with central neck dissection between 2003 and 2004 were enrolled. We divided 147 N1a patients into two groups, such as 96 high-PNR versus 51 low-PNR group according to 50% of PNR, and compared these two groups with N0 group. Results: 7.2% (26/363) recurrences were occurred, and 21/147 (14.3 %) recurrences were on N1a patients, and 5/216 (2.3 %) were on N0 patients. Of these 21 recurrences in N1a stage patients, 20 (95.2 %) recurrences were occurred in high-PNR N1a group and only 1 (4.8 %) recurrence was in low-PNR N1a group. The recurrence of low-PNR N1a group was significantly lower than high-PNR N1a group (Log-rank p value = 0.003), but significantly not different from N0 group (Log-rank p value = 0.889). Although this study was a retrospective non-randomized trial with small number of patients, the 10-year recurrence of omitting RAI in low-PNR N1a patients with less than 50% of PNR were shown to be comparable with 216 N0 low risk patients. Conclusion : Positive node ratio could be a useful predictor of recurrence and useful guidance postoperative management -rather than absolute number of positive node.